İlaç kullanımına bağlı gelişen çene osteonekrozu [medication related osteonecrosis of the jaw (MRONJ)] hakkında ilk makale 2003 yılında yayımlandı. MRONJ, kemik metastazı veya osteoporoz için antirezorptif veya antianjiyojenik ilaç alan hastalarda 8 haftadan uzun süre devam eden, maksillofasiyal alanda mevcut olan nekrotik kemikle karakterizedir. Osteonekroza, en sık çene kemikleri olmak üzere kalça ve diz kemiklerinde de rastlanmaktadır. MRONJ'ye neden olan ilaçlar, metastaz yapan malignansilerde, osteoporoz ve Paget hastalığının tedavisinde tercih edilmektedir. MRONJ vakalarının patofizyolojisi, henüz tam olarak aydınlatılamamış olmakla birlikte bu durum, kemiğin 'remodeling' mekanizmasının değişmesi veya kemik rezorpsiyonunun baskılanması, enfeksiyon, immün sistem yetmezliği, anjiyogenezin inhibisyonu, yumuşak doku toksisitesi, kronik mikrotravmalar ve D vitamini yetersizliğiyle açıklanabilmektedir. Önerilen cerrahi ve konservatif tedavi rejimlerinin uygulanması değişken başarı oranları sağlamıştır. Semptomatik tedavilerin başarısız kaldığı vakalarda, cerrahi debridman, enfekte dişin çekimi, oluşmuş nekrotik kemiğin rezeksiyonu gibi cerrahi girişimler gerekli olabilir. Cerrahi girişimlerin başarı şansını artırmak için piezocerrahi, lazer cerrahisi, plateletten zengin plazma uygulanması, lökosit ve plateletten zengin fibrin (L-PRF) kullanımı, ozon terapisi gibi yöntemler de ek tedavi olarak uygulanabilmektedir. MRONJ tedavisinde belki de en önemli basamak, risk grubundaki hastaları bilinçlendirmek ve MRONJ oluşumunu önlemektir. Mevcut literatürün en iyi kanıt incelemesine dayanan bu derleme, MRONJ'nin önlenmesi, yönetilmesi ve tedavi edilmesine yardımcı olacak açık pratik kılavuzlar ve yeni tedavi yöntemleri sunmaktadır. MRONJ'ye multidisipliner bir yaklaşım benimsenmeli, hastanın yaşam kalitesi ön planda tutulmalıdır.
Anahtar Kelimeler: Çenenin bifosfonatla ilişkili osteonekrozu; osteonekroz; bifosfonatlar
The first article about medication related osteonecrosis of the jaw (MRONJ) was published in 2003. MRONJ is characterized by exposed necrotic bone in the maxillofacial area that persists for more than eight weeks in patients taking antiresorptive or antiangiogenic drugs for bone metastasis or osteoporosis. Osteonecrosis is most commonly seen in the bones of the jaw, hip and knee. Drugs that cause MRONJ are preferred for the treatment of metastasis malignancies, osteoporosis and Paget disease. Although the pathophysiology of MRONJ cases has not been fully elucidated yet, this may be explained by the alteration of bone remodeling mechanism or suppression of bone resorption, infection, inhibition of angiogenesis, soft tissue toxicity, immune system failure, chronic microtrauma and vitamin D deficiency. The application of the recommended surgical and conservative treatment regimens have returned variable success rates. In cases where symptomatic treatments fail; surgical procedures such as surgical debridement, extraction of infected tooth, resection of the necrotic bone may be necessary. To increase the chances of success of surgical interventions; piezosurgery, laser surgery, platelet rich plasma application, leukocyte and platelet rich fibrin use, ozone therapy can also be applied as additional treatment. This review, based on best evidence review of currently available literature provides clear practical guidelines and new treatment methodes to help to prevent, manage and treat MRONJ. All inclusive, a multidisciplinary approach to MRONJ should be adopted, prioritizing patient's quality of life.
Keywords: Biphosphonate-associated osteonecrosis of the jaw; osteonecrosis; bisphosphonates
- Lafforgue P. Pathophysiology and natural history of avascular necrosis of bone. Joint Bone Spine. 2006;73(5):500-7. [Crossref] [PubMed]
- Marx RE, Stern D. Oral and Maxillofacial Pathology: a Rationale for Diagnosis and Treatment. 1st ed. Chicago: Quintessence Pub. Co.,; 2003. p.908.
- Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofacial Surg. 2003;61(9):1115-7. [Crossref] [PubMed]
- Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. American association of oral and maxillofacial surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 2014;72(10):1938-56. [Crossref] [PubMed]
- Duygu Çapar G, Cabbar F, Yalçın GM, Özçakır Tomruk C. [Medication related jaw osteonecrosis: review]. J Dent Fac Atatürk Uni. 2015; Suppl 13;118-29.
- Henien M, Carey B, Hullah E, Sproat C, Patel V. Methotrexate-associated osteonecrosis of the jaw: a report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;124(6):e283-e7. [Crossref] [PubMed]
- Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63(11):1567-75. [Crossref] [PubMed]
- Cummings SR, Martin JS, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756-65. [Crossref] [PubMed]
- Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP, Czerwiński E, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res. 2012;27(3):694-701. [Crossref] [PubMed] [PMC]
- Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;5;377(9768):813-22. [Crossref]
- Stopeck A, Body JJ, Fujiwara Y, Lipton A. 2LBA Denosumab versus zoledronic acid for the treatment of breast cancer patients with bone metastases: results of a randomized phase 3 study. EJC Supplements. 2009;7(3):2-3. [Crossref]
- Baron R, Ferrari S, Graham R, Russell G. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone. 2011;1;48(4):677-92. [Crossref] [PubMed]
- Roelofs AJ, Thompson K, Gordon S, Rogers MJ. Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res. 2006;15;12(20 Pt 2):6222s-30s. [Crossref] [PubMed]
- Russell RG, Rogers MJ. Bisphosphonates: from the laboratory to the clinic and back again. Bone. 1999;25(1):97-106. [Crossref] [PubMed]
- Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004;62(5):527-34. [Crossref] [PubMed]
- Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, et al. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res. 2008;23(6):826-36. [Crossref] [PubMed] [PMC]
- Ripamonti C, Maniezzo M, Campa T, Fagnoni E, Brunelli C, Saibene G, et al. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol. 2009;20(1):137-45. [Crossref] [PubMed]
- Reid IR, Bolland MJ, Grey AB. Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity? Bone. 2007;41(3):318-20. [Crossref] [PubMed]
- Yamashita J, McCauley LK. Antiresorptives and osteonecrosis of the jaw. J Evid Based Dent Pract. 2012;12(3 Suppl):233-47. [Crossref]
- Bi Y, Gao Y, Ehirchiou D, Cao C, Kikuiri T, Le A, et al. Bisphosphonates cause osteonecrosis of the jaw-like disease in mice. Am J Pathol. 2010;177(1):280-90. [Crossref] [PubMed] [PMC]
- Hokugo A, Christensen R, Chung EM, Sung EC, Felsenfeld AL, Sayre JW, et al. Increased prevalence of bisphosphonate‐related osteonecrosis of the jaw with vitamin D deficiency in rats. J Bone Miner Res. 2010;25(6):1337-49. [Crossref] [PubMed] [PMC]
- Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(4):433-41. [Crossref] [PubMed]
- Wood J, Bonjean K, Ruetz S, Bellahcéne A, Devy L, Foidart JM, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther. 2002;302(3):1055-61. [Crossref] [PubMed]
- Ficarra G, Beninati F, Rubino I, Vannucchi A, Longo G, Tonelli P, et al. Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment. J Clin Periodontol. 2005;32(11):1123-8. [Crossref] [PubMed]
- Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC, Janjan NA, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003;1;21(21):4042-57. [Crossref] [PubMed]
- Aguirre JI, Akhter MP, Kimmel DB, Pingel JE, Williams A, Jorgensen M, et al. Oncologic doses of zoledronic acid induce osteonecrosis of the jaw‐like lesions in rice rats (oryzomys palustris) with periodontitis. J Bone Miner Res. 2012;27(10):2130-43. [Crossref] [PubMed] [PMC]
- Kang B, Cheong S, Chaichanasakul T, Bezouglaia O, Atti E, Dry SM, et al. Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice. J Bone Miner Res. 2013;28(7):1631-40. [Crossref] [PubMed] [PMC]
- Hansen T, Kunkel M, Weber A, Kirkpatrick CJ. Osteonecrosis of the jaws in patients treated with bisphosphonates-histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med. 2006;35(3):155-60. [Crossref] [PubMed]
- Lin JH. Bisphosphonates: a review of their pharmacokinetic properties. Bone. 1996;18(2):75-85. [Crossref] [PubMed]
- McGowan K, McGowan T, Ivanovski S. Risk factors for medication‐related osteonecrosis of the jaws: a systematic review. Oral Dis. 2018;24(4):527-36. [Crossref] [PubMed]
- Otto S, Schuler K, Ihrler S, Ehrenfeld M, Mast G. Osteonecrosis or metastases of the jaw or both? Case report and review of the literature.J Oral Maxillofac Surg. 2010;68(5):1185-8. [Crossref] [PubMed]
- Otto S, Hafner S, Grötz KA. The role of inferior alveolar nerve involvement in bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg. 2009;67(3):589-92. [Crossref] [PubMed]
- Yalcin ED, Gungormus M. Cone-beam computed tomography ımaging findings of bisphosphonate-related osteonecrosis of the Jaws (BRONJ): a review article. Int J Dent Sci Res. 2015;3(5):111-5.
- Boeddinghaus R, Whyte A. Trends in maxillofacial imaging. Clin Radiol. 2018;73(1):4-18. [Crossref] [PubMed]
- Hayashida S, Soutome S, Yanamoto S, Fujita S, Hasegawa T, Komori T, et al. Evaluation of the treatment strategies for medication‐related osteonecrosis of the jaws (MRONJ) and the factors affecting treatment outcome: a multicenter retrospective study with propensity score matching analysis. J Bone Miner Res. 2017;32(10):2022-29. [Crossref] [PubMed]
- Marx RE. Oral and Intravenous Bisphosphonate-Induced Osteonecrosis of the Jaws: History, Etiology, Prevention, and Treatment. 2nd ed. Chicago, Ill, USA: Quintessence; 2007. p.160.
- Yildiz A, Esen E, Kürkçü M, Damlar I, Dağlioğlu K, Akova T, et al. Effect of zoledronic acid on osseointegration of titanium implants: an experimental study in an ovariectomized rabbit model. J Oral Maxillofac Surg. 2010;68(3):515-23. [Crossref] [PubMed]
- Abtahi J, Tengvall P, Aspenberg P. Bisphosphonate coating might improve fixation of dental implants in the maxilla: a pilot study. 2010;39(7): 673-7. [Crossref] [PubMed]
- Abtahi J, Tengvall P, Aspenberg P. A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants. 2012;50(5):1148-51. [Crossref] [PubMed]
- Ristow O, Rückscloß T, Müller M, Berger M, Kargus S, Pautke C, et al. Is the conservative non-surgical management of medication-related osteonecrosis of the jaw an appropriate treatment option for early stages? A long-term single-center cohort study. J Craniomaxillofac Surg. 2019;47(3):491-9. [Crossref] [PubMed]
- Yoneda T, Hagino H, Sugimoto T, Ohta H, Takahashi S, Soen S, et al. Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology, and Japanese Society of Oral and Maxillofacial Surgeons. J Bone Miner Metab. 2010;28(4):365-83. [Crossref] [PubMed]
- Ristow O, Otto S, Troeltzsch M, Hohlweg-Majert B, Pautke C. Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ). J Craniomaxillofac Surg. 2015;43(2):290-3. [Crossref] [PubMed]
- Merigo E, Cella L, Aldo Oppici, Arbasi MC, Clini F, Fontana M, et al. Combined approach to treat medication-related osteonecrosis of the jaws. J Lasers Med Sci. 2018;9(2):92-100. [Crossref] [PubMed] [PMC]
- Blus C, Szmukler-Moncler S, Giannelli G, Denotti G, Orrù G. et al. Use of ultrasonic bone surgery (Piezosurgery) to surgically treat bisphosphonate-related osteonecrosis of the jaws (BRONJ). A case series report with at least 1 year of follow-up. Open Dent J. 2013;23;7:94-101. [Crossref] [PubMed] [PMC]
- escovi P, Merigo E, Meleti M, Manfredi M, Fornaini C, Nammour S, et al. Conservative surgical management of stage I bisphosphonate-related osteonecrosis of the jaw. Int J Dent. 2014;2014:107690. [Crossref] [PubMed] [PMC]
- Vescovi P, Giovannacci I, Otto S, Manfredi M, Merigo E, Fornaini C, et al. Medication-related osteonecrosis of the jaw: an autofluorescence-guided surgical approach performed with er: YAG laser. Photomed Laser Surg. 2015;33(8):437-42. [Crossref] [PubMed]
- Atalay B, Yalcin S, Emes Y, Aktas I, Aybar B, Issever H, et al. Bisphosphonate-related osteonecrosis: laser-assisted surgical treatment or conventional surgery? Lasers Med Sci. 2011;26(6):815-23. [Crossref] [PubMed]
- Adornato MC, Morcos I, Rozanski J. The treatment of bisphosphonate-associated osteonecrosis of the jaws with bone resection and autologous platelet-derived growth factors. J Am Dent Assoc. 2007;138(7):971-7. [Crossref] [PubMed]
- Cano-Durán JA, Pe-a-Cardelles JF, Ortega-Concepción D, Paredes-Rodríguez VM, García-Riart M, López-Quiles J, et al. The role of Leucocyte-rich and platelet-rich fibrin (L-PRF) in the treatment of the medication-related osteonecrosis of the jaws (MRONJ). J Clin Exp Dent. 2017;1;9(8):e1051-e9. [PubMed]
- Owosho AA, Estilo CL, Huryn JM, Yom SHK. et al. Pentoxifylline and tocopherol in the management of cancer patients with medication-related osteonecrosis of the jaw: an observational retrospective study of initial case series. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122(4):455-9. [Crossref] [PubMed] [PMC]
- Keskinrüzgar A, Yanık S, Aras MH, Çetiner S. [Teriparatide [parathyroid hormone (1-34)] and dentistry]. Acta Odontol Turc. 2015;32(3):165-70. [Crossref]
- Dyas A, Boughton BJ, Das BC. Ozone killing action against bacterial and fungal species; microbiological testing of a domestic ozone generator. J Clin Pathol. 1983;36(10):1102-4. [Crossref] [PubMed] [PMC]
- Lombard T, Neirinckx V, Rogister B, Gilon Y, Wislet S. Medication-related osteonecrosis of the jaw: new insights into molecular mechanisms and cellular therapeutic approaches. Stem Cells Int. 2016;2016:8768162. [Crossref] [PubMed] [PMC]
- Agrillo A, Filiaci F, Ramieri V, Riccardi E, Quarato D, Rinna C, et al. Bisphosphonate-related osteonecrosis of the jaw (BRONJ): 5 year experience in the treatment of 131 cases with ozone therapy. Eur Rev Med Pharmacol Sci. 2012;16(12):1741-7. [PubMed]
- Vescovi P, Manfredi M, Merigo E. Adjuvant treatment options in the management of medication-related osteonecrosis of the jaw. Medication-Related Osteonecrosis of the Jaws. 2015. p.103-9. [Crossref]
- Rugani P, Acham S, Kirnbauer B, Truschnegg A, Obermayer-Pietsch B, Jakse N. et al. Stage-related treatment concept of medication-related osteonecrosis of the jaw-a case series. Clin Oral Investig. 2015;19(6):1329-38. [Crossref] [PubMed]
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